By correlating the antigenic expression on fetal lymphoid cells with the phenotypic determinant on malignant lymphocytes, we will establish the stage during differentiation at which leukocytes are susceptible to carcinogenic agents. Malignant transformation has been considered an arrest in cell differentiation. Thus, a characterization of neoplastic leukocytes will provide information to determine at what particular stage of normal leukocyte differentiation the neoplastic event occurred. To characterize these fetal and malignant lymphoid cells, more effective and definitive means of identifying leukocyte subpopulations must be developed and utilized. We will examine both surface and cytoplasmic antigenic determinants on individual fetal lymphoid cells and malignant leukocytes, using our double-lable immunoperoxidase technique. We will correlate the presence of subpopulations of cells to their topographic relationship within the tissue with frozen sections, since the spatial distribution of cell types is important in the stages of maturation (e.g., thymus). The monoclonal antibodies used to characterize the fetal and malignant leukocytes will be directed against normal and tumor-associated antigenic determinants (e.g., common acute lymphocytic leukemia antigen). Particular attention will be given to cytoplasmic determinants, since these antigens may not be expressed on the cell surface and thus may go undetected when using immunofluorescence on viable cells (e.g., cytoplasmic mu in pre-B cells). The sequence in maturation will be examined by functional criteria, because the development of immunocompetence is correlated with age and the expression or loss of various antigenic markers. Differentiation-inducing agents (e.g., phorbol ester) will be used to promote differentiation of both fetal and malignant leukocytes. The antigenic expression and function of the cells after culture will be tested. This study will contribute to the basic understanding of the origin of malignancy by identifying the susceptible stage during leukocyte differentiation at which a carcinogenic event has occurred and determine prognosis and treatment, since the course of disease and selection of therapy can be determined by the extent of cell maturation.